Vitamin D Therapy in Individuals with Pre-Hypertension or Hypertension: The DAYLIGHT Trial

Background

Vitamin D deficiency has been associated with a higher risk of cardiovascular disorders, including hypertension [1,2]. Throughout the cardiovascular system vitamin D receptors have been identified, for instance in vascular smooth muscle, endothelium and cardiomyocytes [3,4]. Animal studies have linked receptor disruption to increased levels of blood pressure, which can be normalised by the administration of vitamin D [5].
Since adequately designed studies to investigate the link between vitamin D and blood pressure are limited, the investigators conducted the DAYLIGHT study. This a double-blind, 6-month, controlled, randomised trial. High-dose vitamin D3 supplementation (liquid formulation; 4,000 IU/day) was compared with a low-dose (400 IU/day) in a racially diverse population (aged 18-50 years old) with prehypertension and untreated stage 1 hypertension (120-159 mm Hg) and vitamin D deficiency (25-hydroxyvitamin D levels ≤ 25 ng/ml). The primary endpoint was the change in mean 24-hour ambulatory systolic blood pressure.

Main results

After 6 months, the change in 24-hour systolic blood pressure from baseline was not significantly different between the high-dose and low-dose groups (-0.8 mm Hg vs -1.6 mm Hg, respectively, P=0.71).

In the high-dose group, vitamin D status improved within 2 months (median vitamin D levels at 2-month visit: 33 ng/ml (IQR: 26 to 40) in the high-dose arm versus 20 ng/ml (IQR: 15 to 25) in the low-dose arm (P<0.001), after which it remained stable. At the final visit, 21% of individuals in the high-dose and 48% in the low-dose arm had 25-hydroxyvitamin D < 20 ng/ml.

The association between change in 25-hydroxyvitamin D and change in 24-hour blood pressure was non-significant (Spearman coefficient: -0.05, P=0.34), not even in individuals showing the largest increases in 25-hydroxyvitamine D.

Pre-specified subgroup analyses did not reveal evidence of heterogeneity in the results.

Conclusions

The present study found that vitamin D supplementation is not related to lower blood pressure in individuals with vitamin D deficiency and untreated pre- or stage 1 hypertension. Furthermore, it suggests that the association between vitamin D status and hypertension that has been described in previous observational studies is not causal. The ongoing VITAL study [6] may clarify whether vitamin D supplementation may be beneficial for other cardiovascular risk factors.